Protective role of Bcl-2 on β-amyloid-induced cell death of differentiated PC12 cells: reduction of NF-κB and p38 MAP kinase activation

Song, Youn S.; Park, Hye Ji; Kim, Soo Yeon; Lee, Seung Ho; Yoo, Hyun-jung; Lee, Hee Soon; Lee, Myung Koo; Oh, Ki Wan; Kang, Sun-Kyung; Lee, Seoung Eun; Hong, Jin Tae

doi:10.1016/j.neures.2004.01.010

Cited by 61 publications

(36 citation statements)

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“…Depending on the specific role of NF-κB in apoptosis, it may regulate the expression of either proapoptotic or antiapoptotic Bcl-2 proteins [45]. However, since in SH-SY5Y and in some neuronal cell types NF-κB is more-commonly associated with pro-apoptotic functions [44,46], and because NF-κB activation plays a pro-apoptotic role also in activation of NAD(P)H oxidase and mitochondrial pathways [9], as often observed in the early stages of apoptosis [52]. Here, inhibition of NAD(P)H oxidase blocks activation of MAPKs, suggesting ROS generation upstream to MAPK activation in SH-SY5Y cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

The signalling axis mediating neuronal apoptosis in response to [Pt(O,O′-acac)(γ-acac)(DMS)]

Muscella

Calabriso

Vetrugno

et al. 2011

Biochemical Pharmacology

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Section: Discussionmentioning

confidence: 99%

The signalling axis mediating neuronal apoptosis in response to [Pt(O,O′-acac)(γ-acac)(DMS)]

Muscella

Calabriso

Vetrugno

et al. 2011

Biochemical Pharmacology

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“…In vitro studies show that increasing survival promoting members of the Bcl family, specifically Bcl-2, can protect neuron-like cells from Aβ induced toxicity (Deng et al, 1999); (Saille et al, 1999); (Song et al, 2004). These observations led us to suspect that a similar condition might exist in the transgenic mouse brain.…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection

Karlnoski

Wilcock

Dickey

et al. 2007

Neurobiology of Disease

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Aβ-induced neurodegeneration is limited in APP and APP+PS1 transgenic mice. In middle-aged APP+PS1 transgenic mice, we found significantly increased Bcl-2 expression. The increase in Bcl-2 is restricted to amyloid-containing brain regions and is not found at young ages, suggesting that Aβ deposition is the stimulus for increased Bcl-2. Western blot results were confirmed with immunohistochemistry, and qRT-PCR. In addition, we found that APP transgenic mice were protected from neurotoxicity caused by an injection of bak BH3 fusion peptides, known to induce apoptosis by antagonizing bcl protein activity. Nissl and fluorojade stained slides showed that the active bak BH3 peptide caused substantial neuronal loss in the dentate gyrus and CA3 regions of nontransgenic, but not APP mice. The inactive mutant bak BH3 peptide did not cause degeneration in any mice. These data demonstrate that the increased Bcl-2 expression in brain regions containing Aβ deposits is associated with neuroprotection. KeywordsBax; APP+PS1 transgenic mice; Alzheimer's disease; neurotoxicity; Aβ; apoptosis The amyloid cascade hypothesis states that the dysregulation of amyloid precursor protein (APP) processing and Aβ production are the major causes for neuronal death and dysfunction leading to dementia in Alzheimer's disease (Hardy and Selkoe, 2002). Genetic and environmental factors, such as APP or PS-1 mutations, cause an accumulation of Aβ which forms diffuse and compact plaques. These plaques are thought to cause oxidative stress, activate microglia and astrocytes, causing cytokine release, inflammation and altered ionic homeostasis, culminating in cytotoxicity and neuronal death.The Aβ peptide can directly induce neuronal apoptosis in vitro (Pike et al., 1993); (Hensley et al., 1995); (Schubert and Chevion, 1995); (Wogulis et al., 2005). Intracellular Aβ may activate apoptosis by interacting with the endoplasmic reticulum and endosomes and by binding to alcohol dehydrogenase within the mitochondria (Dickson, 2004). Aβ also induces changes in nitric oxide production and mitochondrial activity facilitating apoptosis (Keil et al., 2004). InCorresponding author: Dave Morgan, Alzheimer Research Laboratory, University of South Florida 12901 Bruce B. Downs Blvd MDC Box 9 Tampa, FL 33612, Scientist.dave@gmail.com Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Aβ-induced neuronal toxicity is limited in the APP transgenic mouse models of AD. A modest reduction in hippocampal neurons was found in old APP23 mice, but the cortical neuron census was unaffected despite extensive amyloid deposition (Calhou...

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“…For example, ERK activation mediates apoptosis induced by anti-cancer drug Zn 2þ , peroxinitrate, and ceramide in neuroblastoma SH-SY5Y cells, dopaminergic PC12 cells, and astrocytes [Blazquez et al, 2000;Seo et al, 2001;Kim et al, 2002]. The activation of PPARg coactivator-1, which activates PPAR-g as well as other nuclear receptors, is positively associated with p38 activity [Puigserver et al, 2001], and interestingly, the overexpression of Bcl-2 can suppress the activation of p38 and subsequently enhance the cell survival [Song et al, 2004]. In our experiment, we have noted that the decreased expression of Bcl-2 and Bcl-w proteins can occur as early as 2 h after TGZ treatment.…”

Section: Discussionmentioning

confidence: 99%

Activation of peroxisome proliferator‐activated receptor‐γ by troglitazone (TGZ) inhibits human lung cell growth

Lee

Mok

et al. 2005

J of Cellular Biochemistry

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Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and a crucial regulator of cellular differentiation. PPAR-gamma ligands have been demonstrated to inhibit growth of several cancer cells. In this study, two human lung cancer cells (NCI-H23 and CRL-2066) and one human lung normal cell (CRL-202) were used for the experiments. The results showed that in consistence with the loss of viability, troglitazone (TGZ) induced apoptosis of CRL-2066 and NCI-H23 cells but not CCL-202 cells. TGZ upregulated PPAR-gamma expression in all the three lung cell lines, especially in the cancer cells. In association of the time-dependent inhibition of the cell proliferation, TGZ downregulated the expression of Bcl-w and Bcl-2 but activated extracellular signal-regulated kinase (ERK)1/2 and p38, suggesting that the growth-inhibitory effect of TGZ is associated with the reduction of Bcl-w and Bcl-2 and the increase of ERK1/2 and p38 activation. SAPK/JNK activation assay showed a decreased activity in all the three cell lines tested after TGZ treatment. It was also demonstrated that TGZ could activate PPAR-gamma transcriptionally. We conclude that TGZ inhibits growth of human lung cancer cells via the induction of apoptosis and the inhibition of cell growth, at least in part, in a PPAR-gamma-relevant manner. The mechanism of TGZ is associated with the activation of ERK and p38, the reduction of SAPK/JNK activity, and the alteration of Bcl-w and Bcl-2.

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Protective role of Bcl-2 on β-amyloid-induced cell death of differentiated PC12 cells: reduction of NF-κB and p38 MAP kinase activation

Cited by 61 publications

References 47 publications

The signalling axis mediating neuronal apoptosis in response to [Pt(O,O′-acac)(γ-acac)(DMS)]

The signalling axis mediating neuronal apoptosis in response to [Pt(O,O′-acac)(γ-acac)(DMS)]

Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection

Activation of peroxisome proliferator‐activated receptor‐γ by troglitazone (TGZ) inhibits human lung cell growth

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